Hemorrhage Clinical Trial
Official title:
The Immunomodulatory Effect of Antrifibrinolytic (Tranexamic Acid) in Total Knee Arthroplasty
The administration of the tranexamic acid (TRAXA), an antifibrinolytic, blocks primary
fibrinolysis, and thus the haemorrhage, in the early postoperative period. Significant
surgical operations, as well as trauma, initiate a similar dynamic homeostatic mechanism
between the creation of a clot (primary and secondary haemostasis) and its dissolution
(fibrinolysis). Antifibrinolytics have been proven effective in reducing haemorrhage in
patients who have undergone significant surgical operations with normal fibrinolysis, with
the use of an appropriate surgical technique.
A pharmacokinetic study has shown that peak fibrinolytic activity is present for 6 hours
after the incision and it persists for 18 hours in total knee and hip arthroplasty. The
administration of the tranexamic acid in optional orthopaedic surgery of total hip (THA) and
knee (TKA) arthroplasty reduces the postoperative haemorrhage, as well as the number and
volume of the postoperative autologous blood.
A trauma in the organism triggers the immunologic response. New term has been introduced -
the post-traumatic immunosuppression (PTI), characterised by: a change on the immunologic
cells (neutrophilia, monocytosis, increased number of mesenchymal stromal cells, reduced
expression of HLA-DR on monocytes, reduced function of natural killer (NK) cells, increased
lymphocyte apoptosis, a shift in homoeostasis towards the Th2 phenotype facilitated by Treg
lymphocytes - CD4+CD25+CD127-); a change in production levels of various cytokines
(anti-inflammatory cytokines): IL-10, IL-4; anti- and pro-inflammatory cytokine: IL-6;
pro-inflammatory cytokines IL-2, TNF-α, IFN-γ); the activation of the complement system (C5a
and C3a via factor VII - tissue factor system, activated by cell damage).
Post-traumatic immunosuppression can be made worse by transfusion, haemorrhage, stress,
significant surgical operation and immunosuppressive drugs.
The research has shown that Treg lymphocytes CD4+CD25+CD127- have an important role in
controlling the acquired and innate immunity (comprising 6-8% of all CD4+ lymphocytes).
Stopping haemorrhage prevents the occurrence of anaemia, as well as the need for transfusion
of blood products, which lead to developing the post-traumatic immunosuppression (PTI).
Status | Recruiting |
Enrollment | 80 |
Est. completion date | December 2019 |
Est. primary completion date | December 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 30 Years to 80 Years |
Eligibility |
Inclusion Criteria: - ASA I/II status - scheduled for endoprosthetic total knee arthroplasty. - laboratory results suitable for elective endoprosthetic surgery: blood panel, coagulation, liver enzymes, kidney function parameters, urine sediment; - patient voluntarily, in accordance with the KBCSM form on the administration of Tranexamic Acid in endoprosthetic total knee arthroplasty, give their consent for its administration. - signed informed consent for transfusion Exclusion criteria: - general anaesthesia - revision arthroplasty - previous blood transfusions - known allergic reaction to TRAXA - presence of an infection and/or acutization of a chronic disease - existing malignant disease - autoimmune disease - hematologic disease - diabetes - renal failure - liver cirrhosis - chronic anticoagulant therapy - analgesia by non-steroidal anti-inflammatory drugs - combined use of the autologous and allogeneic blood postoperatively when the recovery of the autologous blood is insufficient in relation to the haemorrhage. Exclusion Criteria refers to the patients for whom Tranexamic Acid was contraindicated: ----thromboembolic events (IM, CVI, DVT) - known risk of thrombosis or thromboembolic events (thrombogenic valve disease, thrombogenic rhythm disorder, coagulation-hypercoagulation disorder) - epilepsy - patients who use oral contraceptives - known retinal arterial or venous occlusions. To patients who fulfil the participation criteria for the trial in the first selection, and for whom TRAXA is contraindicated in the second selection, blood transfusion will be administered in accordance with the indication. |
Country | Name | City | State |
---|---|---|---|
Croatia | Klinicki Bolnicki Centar Sestre Milosrdnice | Zagreb |
Lead Sponsor | Collaborator |
---|---|
Sisters of Mercy University Hospital | Clinical Hospital Centre Zagreb |
Croatia,
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* Note: There are 19 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | The immunomodulation effect of Tranexamic Acid (IM) | Trial will include approximately 100 patients in total, which will be divided into four groups of 25 patients. The immunomodulation effect is monitored through the analysis of the lymphocyte subpopulation in the peripheral blood through flow cytometry. The result of each lymphocyte subpopulation will be registered as a percentage of all helper cells (CD4+) and all lymphocytes, as well as their absolute number in the peripheral blood. These parameters will be monitored dynamically in the chronological order as shown below: Day 1 - Preoperatively; Day 1 - Postoperatively T1 (IM) K - 6 hrs postoperatively T1 (IM) A - 6 hrs after the first TRAXA dose, and two hours before LMWH T1 (IM) B - 6 hrs postoperatively (after the transfusion of the autologous blood by means of the autotransfusion system); Day 3 - Postoperatively; Day 5 - Postoperatively; Day 7 - Postoperatively; For immunologic testing of each patient's blood 25 ml (5 ml x 5) during 7 days will be sampled. |
two years | |
Secondary | The effect of the Tranexamic Acid on the primary fibrinolysis (F) | The fibrinolytic activity of plasma will be examined through euglobulin lysis time testing Blood sampling follows the same time intervals of blood sampling for determining Treg lymphocytes. Fibrinolysis is monitored until the third postoperative day. In total per patient for analysis of the fibrinolytic activity 15 mL (5 mL x 3) of blood will be sampled during a 3-day period. Day 1 - Preoperatively; Day 3 - Postoperatively T1 (F) K - 6 hrs postoperatively T1 (F) A - 6 hrs after the first TRAXA dose, and two hours before LMWH T1 (F) B - 6 hrs postoperatively (after the transfusion of the autologous blood by means of the autotransfusion system); Day 3 - Postoperatively; |
two years |
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